Physicians now have only vague guidelines for the administration of tricyclic antidepressants to elderly patients. The side effects so common in these patients (especially cardiovascular and CNS) make many physicians reluctant to use these drugs, prompt them to underdose, and to discontinue treatment prematurely. And yet, there are no treatments known that are safer and more effective for elderly depressed patients. Thus, the patient over age 60 is essentially deprived of optimal pharmacotherapy for depression at this time. The proposed research is designed to ascertain, in a double-blind placebo-controlled study, whether plasma levels and/or saliva levels of imipramine, doxepine and/or their demethylated metabolites will be useful in determining appropriate dosages for patients 60 years of age and older. If so, a significant contribution will have been made in assisting the primary care physician as well as the psychiatrist, in planning a rational treatment approach for those older depressed patients whom they wish to treat with tricyclic antidepressants.